Enhanced anti-tumor and anti-metastasis therapy for triple negative breast cancer by CD44 receptor-targeted hybrid self-delivery micelles

Tumor growth and metastasis are multistep processes regulated by multiple signaling pathways. The successful treatment of cancer largely depends on the ability to inhibit metastatic process. Multiphase inhibition of metastasis is a promising approach. Here, we described a targeting delivery system which was constructed by mixing hyaluronic acid-D-alpha-tocopheryl succinate (HA-TOS, HT) and low molecular weight heparin-TOS (LMWH-TOS, LT) to form a stable hybrid micelle (HT-LT), encapsulating chemotherapeutic drug doxorubicin (DOX). The prepared HT-LT NPs was about 125 nm in diameter with high drug encapsulation rate and continuous drug release behavior. We confirmed that HT-LT NPs exhibited an effective targeting ability both in vitro and in vivo using a 4T1 model that was attributed to HA binding to CD44 receptors. In addition, HT-LT NPs acted on different phases of the invasion-metastasis cascade and inhibited tumor cell migration and invasion, thus inhibiting tumor metastasis. This combinatorial strategy provided an alternative approach for triple negative breast cancer therapy.